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Perinatal Domoic Acid as a Neuroteratogen

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Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 29))

Abstract

In mammals, the period shortly before and shortly after birth is a time of massive brain growth, plasticity and maturation. It is also a time when the developing brain is exquisitely sensitive to insult, often with long-lasting consequences. Many of society’s most debilitating neurological diseases arise, at least in part, from trauma around the time of birth but go undetected until later in life. For the past 15 years, we have been studying the consequences of exposure to the AMPA/kainate agonist domoic acid (DOM) on brain development in the rat. Domoic acid is a naturally occurring excitotoxin that enters the food chain and is known to produce severe neurotoxicity in humans and other adult wildlife. Our work, and that of others, however, has demonstrated that DOM is also toxic to the perinatal brain and that toxicity occurs at doses much lower than those required in adults. This raises concern about the current regulatory limit for DOM contamination that is based on data in adult animals, but has also allowed creation of a novel model of neurological disease progression. Herein, we review briefly the toxicity of DOM in adults, including humans, and describe features of the developing nervous system relevant to enhanced risk. We then review the data on DOM as a prenatal neuroteratogen and describe in detail the work of our respective laboratories to characterize the long-term behavioural and neuropathological consequences of exposure to low-dose DOM in the newborn rat.

The original version of this chapter was revised. Incorrect co-author name has been corrected. The correction to this chapter is available at https://doi.org/10.1007/978-3-319-34136-1_67

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Notes

  1. 1.

    Due to the profound neurological consequences of DOM intoxication, including the unusual observation of anterograde amnesia in more severely affected individuals, the syndrome was subsequently termed “amnesic shellfish poisoning (ASP)”.

  2. 2.

    In the rat, the blood–brain barrier develops progressively, commencing on around gestational day 15 or 20 and showing mature morphological characteristics and structural integrity on approximately postnatal day 24 (reviewed in Kaufmann 2000).

  3. 3.

    Moshe et al. (1983) have argued that age differences in EAA-induced seizures may relate to the precocious development of excitatory systems within the limbic region which develop prenatally, with concurrently delayed inhibitory mechanisms—not functionally mature until after two weeks of age.

  4. 4.

    US Patents 7034201B2, 7521589 and 7622101 and Canadian Patent CA2448647.

  5. 5.

    Adolescence is a developmental time period wherein the typical rat is exquisitely sensitive to the rewarding properties of nicotine.

  6. 6.

    Assessed using entries to repeat (ERT); a reliable measure of choice accuracy in the RAM.

  7. 7.

    Reference memory can be considered to be reflected as an inability to recall the overall “rules” of the test procedure (i.e. in these circumstances, each arm must be entered once and only once).

  8. 8.

    A reversal task is one in which the platform is relocated to a new quadrant after a set number of trials. Its use in MWM testing has become commonplace as it tends to be more sensitive to subtle deficits produced by experimental intervention (McNamara and Skelton 1993).

  9. 9.

    A probe trial is one in which after a period of time following the final swim trial, the platform is removed from the maze and rats are given a single swim trial in which they move freely in the maze for a set amount of time. Later analyses of this trial generally include time spent in target quadrant (i.e. area in which the platform was most recently located) and the number of annulus crossings; both assessments are used as indices of memory.

  10. 10.

    While PPI deficits are apparent in both male and female DOM-treated rats, it should be noted that the effects of early DOM treatment were in fact impacted upon by both sex and time of day.

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Acknowledgements

Research attributed to the Doucette and Tasker laboratories was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes of Health Research (CIHR), Atlantic Innovation Fund (AIF), Springboard Atlantic and Innovation PEI. T.A. Doucette holds the Jeanne and J Louis Levesque Research Professorship and receives partial salary support from Neurodyn Life Sciences Inc.

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Authors and Affiliations

  1. Department of Psychology, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, C1A4P3, Canada

    Tracy A. Doucette

  2. Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, C1A4P3, Canada

    R. Andrew Tasker

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  1. Tracy A. Doucette
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Correspondence to R. Andrew Tasker .

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Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

  2. Department of Psychology, University of Gothenburg, Gothenburg, Sweden

    Trevor Archer

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Doucette, T.A., Tasker, R.A. (2015). Perinatal Domoic Acid as a Neuroteratogen. In: Kostrzewa, R.M., Archer, T. (eds) Neurotoxin Modeling of Brain Disorders—Life-long Outcomes in Behavioral Teratology. Current Topics in Behavioral Neurosciences, vol 29. Springer, Cham. https://doi.org/10.1007/7854_2015_417

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